Role of the receptor tyrosine kinase Axl in hepatocellular carcinoma and its clinical relevance.

The receptor tyrosine kinase Axl and its ligand Gas6 regulate fundamental biological processes, including cell proliferation, survival and motility, through multiple downstream signaling pathways. Evidence to date suggests that aberrant Axl expression frequently occurs in many malignancies, including hepatocellular carcinoma, and that this is critical for promoting cell proliferation, migration, angiogenesis and metastasis. Moreover, deregulated Axl expression or activation is reportedly associated with resistance to cancer drugs and targeted cancer therapies. Thus, Axl inhibitors may represent a novel therapeutic approach for cancer treatment. This Review summarizes the latest advances concerning the biological role of Axl in hepatocellular carcinoma and its potential clinical relevance.

Circular RNAs in hepatocellular carcinoma: Recent advances.

Circular RNAs (circRNAs) have covalently closed loop structures at both ends, exhibiting characteristics dissimilar to those of linear RNAs. Emerging evidence suggests that aberrantly expressed circRNAs play crucial roles in hepatocellular carcinoma (HCC) by affecting the proliferation, apoptosis and invasive capacity of HCC cells. Certain circRNAs may be used as biomarkers to diagnose and predict the prognosis of HCC. Therefore, circRNAs are expected to become novel biomarkers and therapeutic targets for HCC. Herein, we briefly review the characteristics and biological functions of circRNAs, focusing on their roles in HCC to provide new insights for the early diagnosis and targeted therapy of HCC.

Recent progress in molecular mechanisms of postoperative recurrence and metastasis of hepatocellular carcinoma.

Hepatectomy is currently considered the most effective option for treating patients with early and intermediate hepatocellular carcinoma (HCC). Unfortunately, the postoperative prognosis of patients with HCC remains unsatisfactory, predominantly because of high postoperative metastasis and recurrence rates. Therefore, research on the molecular mechanisms of postoperative HCC metastasis and recurrence will help develop effective intervention measures to prevent or delay HCC metastasis and recurrence and to improve the long-term survival of HCC patients. Herein, we review the latest research progress on the molecular mechanisms underlying postoperative HCC metastasis and recurrence to lay a foundation for improving the understanding of HCC metastasis and recurrence and for developing more precise prevention and intervention strategies.

Role of long noncoding RNA-mediated competing endogenous RNA regulatory network in hepatocellular carcinoma.

Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) are noncoding RNAs (ncRNAs) that occupy over 90% of the human genome, and their main function is to directly or indirectly regulate messenger RNA (mRNA) expression and participate in the tumorigenesis and progression of malignances. In particular, some lncRNAs can interact with miRNAs as competing endogenous RNAs (ceRNAs) to modulate mRNA expression. Accordingly, these RNA molecules are interrelated and coordinate to form a dynamic lncRNA-mediated ceRNA regulatory network. Mounting evidence has revealed that lncRNAs that act as ceRNAs are closely related to tumorigenesis. To date, numerous studies have established many different regulatory networks in hepatocellular carcinoma (HCC), and perturbations in these ceRNA interactions may result in the initiation and progression of HCC. Herein, we emphasize recent advances concerning the biological function of lncRNAs as ceRNAs in HCC, with the aim of elucidating the molecular mechanism underlying these HCC-related RNA molecules and providing novel insights into the diagnosis and treatment of HCC.

Long non-coding RNAs in hepatocellular carcinoma: Potential roles and clinical implications.

Long non-coding RNAs (lncRNAs) are a subgroup of non-coding RNA transcripts greater than 200 nucleotides in length with little or no protein-coding potential. Emerging evidence indicates that lncRNAs may play important regulatory roles in the pathogenesis and progression of human cancers, including hepatocellular carcinoma (HCC). Certain lncRNAs may be used as diagnostic or prognostic markers for HCC, a serious malignancy with increasing morbidity and high mortality rates worldwide. Therefore, elucidating the functional roles of lncRNAs in tumors can contribute to a better understanding of the molecular mechanisms of HCC and may help in developing novel therapeutic targets. In this review, we summarize the recent progress regarding the functional roles of lncRNAs in HCC and explore their clinical implications as diagnostic or prognostic biomarkers and molecular therapeutic targets for HCC.

Genetic alterations in hepatocellular carcinoma: An update.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Although recent advances in therapeutic approaches for treating HCC have improved the prognoses of patients with HCC, this cancer is still associated with a poor survival rate mainly due to late diagnosis. Therefore, a diagnosis must be made sufficiently early to perform curative and effective treatments. There is a need for a deeper understanding of the molecular mechanisms underlying the initiation and progression of HCC because these mechanisms are critical for making early diagnoses and developing novel therapeutic strategies. Over the past decade, much progress has been made in elucidating the molecular mechanisms underlying hepatocarcinogenesis. In particular, recent advances in next-generation sequencing technologies have revealed numerous genetic alterations, including recurrently mutated genes and dysregulated signaling pathways in HCC. A better understanding of the genetic alterations in HCC could contribute to identifying potential driver mutations and discovering novel therapeutic targets in the future. In this article, we summarize the current advances in research on the genetic alterations, including genomic instability, single-nucleotide polymorphisms, somatic mutations and deregulated signaling pathways, implicated in the initiation and progression of HCC. We also attempt to elucidate some of the genetic mechanisms that contribute to making early diagnoses of and developing molecularly targeted therapies for HCC.

Latest developments in precancerous lesions of hepatocellular carcinoma.

Hepatocarcinogenesis in human chronic liver diseases is a multi-step process in which hepatic precancerous lesions progress into early hepatocellular carcinoma (HCC) and progressed HCC, and the close surveillance and treatment of these lesions will help improve the survival rates of patients with HCC. The rapid development and extensive application of imaging technology have facilitated the discovery of nodular lesions of ambiguous significance, such as dysplastic nodules. Further investigations showed that these nodules may be hepatic precancerous lesions, and they often appear in patients with liver cirrhosis. Although the morphology of these nodules is not sufficient to support a diagnosis of malignant tumor, these nodules are closely correlated with the occurrence of HCC, as indicated by long-term follow-up studies. In recent years, the rapid development and wide application of pathology, molecular genetics and imaging technology have elucidated the characteristics of precancerous lesions. Based on our extensive review of the relevant literature, this article focuses on evidence indicating that high-grade dysplastic nodules are more likely to transform into HCC than low-grade dysplastic nodules based on clinical, pathological, molecular genetic and radiological assessments. In addition, evidence supporting the precancerous nature of large cell change in hepatitis B virus-related HCC is discussed.

Expression of c-erbB-2 and glutathione S-transferase-pi in hepatocellular carcinoma and its adjacent tissue.

AIM: To investigate the possible role of c-erbB-2 and glutathione S-transferase (GST-Pi) in primary hepatocellular carcinogenesis and the relationship between liver hype-rplastic nodule (LHN), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). METHODS: The expression of c-erbB-2 and GST-Pi was detected immunohistochemically in 41 tissue specimens of HCC and 77 specimens of its adjacent tissue. RESULTS: The positive expression of c-erbB-2 in LHN (28.6%) was significantly higher than that in LC (0%) (P = 0.032<0.05), but no significant difference was seen between HCC and LHN or LC (P>0.05, chi2= 0.002, 3.447). The positive expression of GST-Pi in HCC (89.6%) or LHN (71.1%) was significantly higher than that in LC (22.9%, P<0.001, chi2= 49.91, 16.96). There was a significant difference between HCC and LHN (P<0.05, chi2= 6.353). CONCLUSION: The c-erbB-2 expression is an early event in the pathogenesis of HCC. GST-Pi may be a marker enzyme for immunohistochemical detection of human HCC and its preneoplastic lesions. LHN seems to be a preneoplastic lesion related to hepatocarcinogenesis.

Management of hepatocellular carcinoma: Predictive value of immunohistochemical markers for postoperative survival.

Hepatocellular carcinoma (HCC) accounts for over 90% of all primary liver cancers. With an ever increasing incidence trend year by year, it has become the third most common cause of death from cancer worldwide. Hepatic resection is generally considered to be one of the most effective therapies for HCC patients, however, there is a high risk of recurrence in postoperative HCC. In clinical practice, there exists an urgent need for valid prognostic markers to identify patients with prognosis, hence the importance of studies on prognostic markers in improving the prediction of HCC prognosis. This review focuses on the most promising immunohistochemical prognostic markers in predicting the postoperative survival of HCC patients.

Expression of p53 and C-myc genes and its clinical relevance in the hepatocellular carcinomatous and pericarcinomatous tissues.

AIM: To investigate the possible roles of p53 and C-myc genes in the primary hepatocellular carcinogenesis and the relationship between the liver hyperplastic nodule (LHN) and hepatocellular carcinoma(HCC). METHODS: The expression of p53 and C-myc genes was detected immunohistochemically in 73 and 60 cases of HCC and pericarcinomatous tissues, respectively. RESULTS: The positive expression of p53 in HCC was significantly higher than that in pericarcinomatous tissues (P<0.05). In pericarcinomatous tissues, the p53 expression was observed only in LHN, but not in liver cirrhosis (LC) and normal liver tissues. The positive expression rate of C-myc in HCC or LHN was significantly higher than that in LC or normal liver tissues (P<0.05 and P<0.01), however, no significant difference was found between HCC and LHN (P>0.05). The positive expression rate of p53 and C-myc in HCC was correlated with the histological differentiation, that in the poorly differentiated was significantly higher than that in well differentiated samples (P<0.05). CONCLUSION: The overexpression of p53 and C-myc genes might play a role in the carcinogenesis of HCC; And LHN seems a preneoplastic lesion related to hepatocarcinogenesis; No evidence supports that LC contribute directly to the hepatocarcinogenesis.